Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions.
Glucagon-like peptide-1 (7-36 amide) (GLP-1) is known to increase insulin release when given as a bolus in the fasted and fed state. GLP-1 also increases glucose uptake and lipid synthesis in cultured adipocytes. In this study we investigated the effects of GLP-1 on glucose uptake and on the levels of expression of the facilitative glucose transporters, GLUT1 and GLUT4, in fully differentiated 3T3-L1 adipocytes. Cells were incubated with GLP-1 (10 nM) with or without insulin (10 and 100 nM) for 24 h. Under these conditions, GLP-1 alone caused an increase in basal and acute insulin-stimulated glucose uptake along with an increase in GLUT1 and GLUT4 protein levels. However, there was no change in the expression of GLUT1 and GLUT4 mRNAs. In the absence of GLP-1, prolonged exposure to insulin caused a marked reduction in the levels of GLUT4 mRNA and protein, and an inhibition of glucose uptake after an acute exposure to insulin. This insulin-induced down-regulation of GLUT4 was prevented when GLP-1 was present during the 24-h treatment. In contrast, the acute insulin-stimulated glucose uptake could not be restored by GLP-1. GLP-1 is therefore the first gut hormone shown to be capable of modulating glucose transporter levels in cultured adipocytes.
Wang
Y
Y
National Institute on Aging/Gerontology Research Center, Diabetes Section, Baltimore, Maryland 21224, USA.
Kole
H K
HK
Montrose-Rafizadeh
C
C
Perfetti
R
R
Bernier
M
M
Egan
J M
JM
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006601:Hexoses / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D011498:Protein Precursors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006601:Hexoses; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D003847:Deoxyglucose; D000242:Cyclic AMP; D011972:Receptor, Insulin